It is widely accepted that the autonomic nervous system can induce and/or worsen cardiac arrhythmias during bouts of myocardial ischemia and infarction. The purpose of the proposed experiments is, first, to define and then characterize how, when, and to what extent changes in nerve traffic, recorded from the discrete thoracic cardiac nerves of the dog, may disrupt the electrical stability of an infarcting heart. The hypothesis considers that the extent and severity of both the early and the delayed ventricular arrhythmias that occur during a myocardial infarction depend upon characteristic sequential changes in autonomic activities to the heart and that the nature and relative contributions of individual autonomic nerve activities are different but predictable. The hypothesis further considers that part of the mode of action of widely-used antiarrhythmic drugs is achieved through modulation of these complex autonomic influences. Simultaneous recordings of sympathetic and parasympathetic autonomic activities will and analyzed before and during a three hour occlusion of a coronary artery. All experiments will be performed in dogs because we can reliably identify all discrete thoracic cardiac nerves and because we can accurately determine their respective regional functional innervation patterns. These experiments will not only provide a quantitative assessment of the changing neural activities that accompany myocardial ischemia but, with this data, we will be able to determine when differences in nerve traffic to the ischemic versus the non-ischemic zone constitute an """"""""autonomic imbalance"""""""". Special experiments will then be performed using a variety of combinations of sympathetic and parasympathetic efferent nerve stimulation to mimic """"""""autonomic imbalance""""""""; before and during coronary artery occlusion. These experiments will, for the first time, quantitatively evaluate autonomic imbalance during acute myocardial ischemia. Also, we expect to prove or disprove whether and, if so, how often autonomic imbalance precipitates cardiac arrhythmias. Together with these experiments that are designed to examine how certain arrhythmic agents modulate autonomic imbalance we expect to generate important new information concerning the mode of action of these antiarrhythmic compounds. Knowledge of how antiarrhythmic changes influence the autonomic control of the heart will not only greatly facilitate the selection of the most appropriate antiarrhythmic compound but it will help minimize the proarrhythmic tendencies in these compounds.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037289-04
Application #
3352836
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Hageman, G R; Simor, T (1993) Attenuation of the cardiac effects of cocaine by dizocilpine. Am J Physiol 264:H1890-5
Gantenberg, N S; Hageman, G R (1992) Cocaine-enhanced arrhythmogenesis: neural and nonneural mechanisms. Can J Physiol Pharmacol 70:240-6
Gantenberg, N S; Hageman, G R (1992) Enhanced induction of ventricular arrhythmias during sympathetic stimulation before and during coronary artery occlusion. Int J Cardiol 34:75-83
Radding, W; Hageman, G R; Gantenberg, N S et al. (1992) A novel acetylcholine receptor-related peptide blocks canine cardiac ganglia and inhibits the nicotinic receptor of PC-12 cells. J Auton Nerv Syst 40:161-9
James 3rd, J C; Gantenberg, N S; Hageman, G R (1990) A sample computer system for physiological data acquisition and analysis. Comput Biol Med 20:407-13
Neely, B H; Hageman, G R (1990) Differential cardiac sympathetic activity during acute myocardial ischemia. Am J Physiol 258:H1534-41
Neely, B H; Hageman, G R (1990) Effects of deafferentation or sequential occlusions on cardiac sympathetic activity during ischemia. Am J Physiol 258:H1542-9